Towards tumour targeting with copper-radiolabelled macrocycle–antibody conjugates: synthesis, antibody linkage, and complexation behaviour

Abstract

A set of four tetra-azamacrocyclic ligands bearing aminomethylphenyl substituents have been prepared and may be attached to a monoclonal antibody via an intermediate thiol-specific vinylpyridine linker molecule. The resultant conjugates may be efficiently radiolabelled with 64Cu or 67Cu at pH 4 to minimise non-specific protein binding, and the copper labelled antibody-conjugate is stable with respect to copper loss in vivo. The forward rate of copper binding has been optimised through a kinetic analysis using stopped-flow spectrophotometry. In succinate buffer, anionic copper species Cu(succ)22–(log β= 4.35) and HCu(succ)2–(log β= 9.64) are the kinetically significant copper species in the pH range 3.6–5.6.