Endocrine Abstracts

Radioactive isotopes of copper are of interest in the development of imaging agents for positron emission tomography (PET) and companion therapeutics. The synthesis of a ligand, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), designed to form stable complexes with radioactive copper isotopes that can be tethered to tumour targeting peptides and antibodies will be presented.

The MeCOSar ligand has been conjugated to Tyr³-octreotate and the conjugate radiolabelled with ⁶⁴Cu^II to form ⁶⁴CuSarTATE. In vitro and in vivo evaluation of ⁶⁴CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2) resulting in with high-quality PET images with excellent tumour to background ratios at 24 h post injection.

The use of MeCOSar to radiolabel antibodies will also be discussed. Attaching the chelator to the antibody or fragment requires careful consideration to avoid compromising the affinity of the antigen-binding site for the target. The use of enzyme-mediated bioconjugation for the site-specific incorporation of a radioactive metal complex into antibodies will be presented. The chemistry presented opens up opportunities for combined imaging and therapy using a combination of ⁶⁴Cu^II- and ⁶⁷Cu^II complexes.