Synthesis and binding affinities of Re(I) and (99m)Tc(I)-containing 16alpha-substituted estradiol complexes: Models for potential breast cancer imaging agents.

To develop technetium and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors, we have synthesized tridentate metal tricarbonyl chelates substituted at the 16alpha-position of estradiol. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or elemental analysis. The rhenium complex 7b showed the highest ER binding affinity (RBA=25.7) among these compounds, so ligand 6b was selected to be labeled by the precursor [(99m)Tc(H(2)O)(3)(CO)(3)](+) to yield technetium(I)-99m complex 7b' with good radiochemical yields. The lipophilicity of corresponding technetium(I)-99m complex 7b' was appropriately reduced, which might be favorable to target tissue selectivity in vivo. The stability of complex 7b' is excellent in 1mM histidine, 1mM cysteine, PBS and bovine serum within 6h in vitro. Copyright 2010 Elsevier Inc. All rights reserved.