Synthesis of Cyclen-Based Copper Complexes as a Potential Estrogen Receptor Ligand / 핵의학분자영상

ABSTRACT

PURPOSE: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using [18F] labeled estrogen ligands, especially [18F]FES. However, [18F] has relatively short-lived half-life (t1/2=1.8 h) and the labeling yield of radio-fluorination is usually low compared with 64Cu (t1/2=12.7 h). 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. MATERIALS AND METHODS: 1,7-Protected cyclen, 1,7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). RESULTS: The prepared ligand 1 was fully characterized by 1H, 13C NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes [Cu(1)]2+2(ClO4-) and [Cu(1)Cl]+Cl- which were confirmed by high-resolution mass (FAB). CONCLUSION: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(II) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.