• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.326-334
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• 2007

Purpose: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using $[^{18}F]$ labeled estrogen ligands, especially $[^{18}F]FES$. However, $[^{18}F]$ has relatively short-lived half-life ($t_{1/2}$ =1.8 h) and the labeling yield of radio-fluorination is usually low compared with $^{64}Cu\;(t_{1/2}=12.7\;h)$. 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 $^1H,\;^{13}C$ NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes $[Cu(1)]^{2+}2(CIO_4^-)\;and\;[Cu(1)Cl]^+Cl^-$ 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(ll) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.